In accordance with 37 C.F.R. §1.52(e)(5), Applicants enclose herewith the Sequence Listing for the above-captioned application entitled “SEQUENCE LISTING”, created on May 18, 2011. The Sequence Listing is made up of 5,153 bytes, and the information contained in the attached “SEQUENCE LISTING” is identical to the information in the specification as originally filed. No new matter is added.
Counter Current purification systems are purification systems where the solid phase moves against the current of the fluid stream either physically or is simulated to make this movement counter current relative to the fluid stream by the change in positioning of different separation beds of the system. Counter Current purification systems include e.g. Simulated Moving Bed chromatography (SMB) and Multicolumn Counter Current Solvent Gradient Purification (MCSGP).
Simulated moving bed chromatography (SMB) was first described in U.S. Pat. No. 2,985,589. The specification discloses a separation tower divided into a number of individual interconnected separation beds containing solid phase chromatography sorbent. An inline pump at the bottom of the tower connects flow from the bottom to the top, thereby providing a continuous loop. Inlet ports for Feedstock (F) and Desorbent (D) and exit ports for Raffinate (R) and Extract (E) are placed at specific points in the series of separation beds. At defined intervals, the position of the beds is switched in the opposite direction from the flow, producing a counter current movement of the solid phase beds relative to the fluid streams. Feedstock (F) introduced into the first bed begins to separate into the various components contained therein, with the less retained species migrating in the direction of fluid flow and being collected at the Raffinate port. The more retained species remain preferentially associated with the solid phase and are collected at the Extract port. By regulating the switch times and flow rates of F, D, R, and E, a cyclic steady state is established, allowing for continuous flow of purified products from the system.
More recently SMB has been applied to separate sugar isomers, hydrocarbons, solvents, and other industrial applications. Many of these industrial devices, like the original '589 device, employ variations of mechanical rotary valves in effecting column switching. The valve components are arranged so that at any given valve position, multiple inlet and outlet flows are directed to predetermined columns, and advanced one position correspondingly with each rotational step. Such rotary valves are disclosed in U.S. Pat. Nos. 6,719,001, 4,574,840, and 4,614,205. To emphasize the intended scale of some of these devices, refer to U.S. Pat. No. 3,040,777 which describes a valve occupying an area of 64 sq. feet and weighing 10 tons.
Other SMB systems are disclosed in U.S. Pat. No. 4,434,051 and U.S. Pat. No. 5,635,072. Another patent, U.S. Pat. No. 6,544,413, discloses a plural valve device having clustered valve assemblies of four valves for control of inputs/outputs proximately to each chromatographic bed. It has the advantage of reducing the volume of liquid for small scale SMB systems. U.S. Pat. No. 6,979,402 discloses a device in which cross-over conduits are replaced entirely by connecting channels machined into the top and bottom plates of the rotary valve body and aligned with column ports to create an SMB fluid loop, thus reducing the void volume.
Several recent applications of SMB to the purification of pharmaceutically active diastereomers and enantiomers have been disclosed in U.S. Pat. Nos. 6,462,221, 6,461,858, 6,458,995, and 6,455,736. The use of new chiral resins in SMB for binary separations of such molecules is becoming commonplace. SMB is also considered for purification of biomolecules from complex mixtures. For example, the purification of monoclonal antibodies using SMB has been reported by Gottschlich et al. (J. Chromatogr. A, 765 (1997) 201) and disclosed in WO 2004/024284. SMB purification has previously been published for insulin purification, as disclosed in WO 2001/087924.
WO 2008/048395 discloses small-scale simulated moving bed chromatography.
Glucagon Like Peptides-1 (GLP-1) is a hormone that is released when the blood sugar level is low. GLP-1 increases the insulin production and thereby reduces the blood sugar level. GLP-1 and GLP-1 analogues are used in the treatment of type II diabetes.
There is still a need for a purification system for purifying a fluid mixtures comprising one or more impurities and a protein or peptide of interest such as a GLP-1 peptide, where the concentration of the impurities is much smaller than the concentration of the protein or peptide of interest.